1. Field of the Invention
The present invention is directed to a non-invasive device and method for detecting possible carbon monoxide poisoning by determining the percentage of carboxyhemoglobin (CO-Hgb) in the subject""s blood. The non-invasive device for determining the percentage of carboxyhemoglobin in blood is a pulse oximeter modified to discriminate between oxy- and carboxyhemoglobin. Preferably the device works in two modes. The first mode is a conventional pulse oximeter capable of determining the level of oxy-hemoglobin (hemoglobin saturated with oxygen) in the subject""s arterial blood. Upon the achievement of certain criteria, described below, the preferred embodiment of the inventive device would switch to a second mode, in which mode the device would be capable of determining carboxyhemoglobin levels.
The device is used in a method for measuring carboxyhemoglobin which includes having the subject breathe oxygen to convert reduced hemoglobin to oxy-hemoglobin, thereby removing reduced hemoglobin as a blood constituent, determining the concentration of the principle two remaining hemoglobin constituents in the blood (oxy- and carboxy) and measuring carboxyhemoglobin by the modified pulse oximeter.
2. Description of the Prior Art
Carbon monoxide (CO) poisoning is an important cause of morbidity and mortality in the United States that often goes unsuspected and therefore is not promptly treated. Sadovnikoff N, Varon J, Sternbach G L, Carbon monoxide poisoning: an occult epidemic, Postgraduate Medicine, 92:86-96 (1992)(incorporated by reference); Kales S N, Carbon monoxide intoxication, Am Fam Phys, 48:1100-4 (1993)(incorporated by reference). CO intoxication is the leading cause of death by poisoning in the U.S. and accounts for approximately 3,800 accidental and suicidal deaths annually. Nonlethal CO poisoning occurs as well, but statistics are not available on the number of incidents of such occurrences. Occult CO poisoning is a type of subacute poisoning caused by an unrecognized source of CO in the home or other indoor environment. Many nonlethal exposures go undetected.
Smoke inhalation from fires accounts for the majority of CO exposure. Firefighters are at high risk. Other sources include furnaces, gas-powered engines, pool heaters and wood stoves.
CO combines preferentially with hemoglobin to produce carboxyhemoglobin, displacing oxygen and reducing systemic arterial oxygen content. CO binds reversibly to hemoglobin with an affinity more than 200 times that of oxygen. Inhaled CO rapidly diffuses across the alveolar-capillary membranes into the bloodstream, where the reversible binding with hemoglobin occurs and carboxyhemoglobin is formed. Carboxyhemoglobin decreases the amount of hemoglobin available for oxygen transport and also results in decreased release of oxygen to tissues.
Symptoms of acute CO poisoning are more dramatic than those of chronic exposure. Subacute or chronic CO poisoning may present less characteristic symptoms and patients may initially be misdiagnosed. The most common misdiagnosis is xe2x80x9cflu-likexe2x80x9d syndrome. At low carboxyhemoglobin levels in chronic CO poisoning, chronic cardiopulmonary problems may be exacerbated. Therefore, chest pains caused by reduced myocardial oxygen delivery due to CO poisoning may be misdiagnosed.
Acute exposure to CO correlates to various symptoms. At carboxyhemoglobin levels of above 10% the victim may be asymptomatic or have a headache. At 20%, CO exposure causes dizziness, confusion and nausea. Between 20 and 50% carboxyhemoglobin levels, the subject experiences visual disturbances, confusion and syncope. At levels above 50% the subject experiences seizures and coma, and death is likely at levels of carboxyhemoglobin above 60%. Sublethal acute exposure leaves some victims with permanent neurologic sequelae.
When CO poisoning is suspected, the diagnosis is usually established either by detection of abnormally high CO in expired air or by analysis of arterial or venous blood for carboxyhemoglobin. Both of these techniques require instrumentation that is not readily available to paramedics or emergency rooms. In addition, because of the lapse of time between the exposure and the test, confirming the diagnosis may be difficult in some patients. Carboxyhemoglobin levels as tested by the lab may be low or undetectable because of the time elapsed between the exposure and taking of the sample.
The analysis of arterial and venous blood samples requires taking a blood sample by arterial or veni puncture or by finger prick, which raises small, but important concerns regarding pain and the potential for transmission of infectious disease, such as vial hepatitis and human immunodeficiency virus (HIV) infection. In addition, analysis of the arterial or venous blood sample is usually done by spectrophotometric means, as disclosed in U.S. Pat. Nos. 4,997,769 and 5,491,341. Such analytic methods require bulky instrumentation.
Tests done after the exposure must be treated with caution. While elevated carboxyhemoglobin levels found by testing blood samples will confirm the diagnosis of CO intoxication, low and moderately increased values must be interpreted with caution. The half-life of carboxyhemoglobin is about four hours when breathing room air and about one hour when breathing pure oxygen. Thus, the carboxyhemoglobin level obtained upon taking the blood sample must be used to extrapolate to the patient""s peak level.
The recent marketing of inexpensive home ambient air CO monitors has increased the frequency with which CO poisoning is reported, many times inaccurately. The increase of such reports requires an increase in EMS visits to investigate. For example, during two cold spells in 1994, the Chicago Fire Department logged over 50,000 calls for suspected CO poisoning, most of which were not corroborated, and many of which resulted in Emergency Room visits to exclude CO intoxication.
The subject must be removed from the source of CO if exposure is suspected. Supplemental oxygen, ventilatory support and monitoring for cardiac arrhythmias are the mainstays of therapy for CO poisoning. Administration of 100% oxygen is usually done as soon as CO poisoning is suspected and before laboratory confirmation is obtained. Since many hospitals send blood samples to distant labs for analysis of carboxyhemoglobin levels, the treating physician must initiate treatment empirically.
Transportation to an appropriate center for hyperbaric oxygen therapy is a method of treatment in severe cases. Hyperbaric oxygen at a pressure of 3 atmospheres reduces the elimination half-life of carboxyhemoglobin to less than 30 minutes and can dissolve enough oxygen to sustain life even in the absence of hemoglobin. In such severe cases of CO poisoning, time is of the essence. There are a limited number of hyperbaric oxygen centers available. The location of a suitable center and transportation of the subject can take some time. Therefore, waiting for lab analysis can be a severe limitation on the treatment of such a subject.
Typical lab analyses include analysis by CO-oximeters and/or gas chromatography. However, as stated above, the drawbacks of relying on these methods are the need to draw arterial blood and the prolonged delay between sample acquisition and the availability of the laboratory results. CO-oximeters are laboratory instruments that measure oxy-, reduced-, carboxy-, and met-hemoglobins (and sometimes also sulf-hemoglobin) in blood samples by analyzing absorbance at multiple wavelengths, chosen to optimally separate the various types of hemoglobin. Mahoney J J, Vreman H J, Stevenson D K, Van Kessel A L. Measurement of carboxyhemoglobin and total hemoglobin by five specialized spectrophotometers (CO-oximeters) in comparison with reference methods, Clinical Chemistry, 39:1693-1700 (1993)(incorporated by reference); Steinke J M, Shepherd A P, Effects of temperature on optical absorbance spectra of oxy-, carboxy-, and deoxyhemoglobin, Clinical Chemistry, 38:1360-4 (1992)(incorporated by reference); Zijlstra W G, Buursma A, Zwart A, Performance of an automated six-wavelength photometer (Radiometer OSM3) for routine measurement of hemoglobin derivatives, Clinical Chemistry, 34:149-52 (1988)(incorporated by reference). CO-oximeters are commercially available from manufacturers such as Radiometer Als, Instrumentation Laboratories and Ciba-Coming.
CO-oximetry is not a non-invasive method of measuring blood constituents, inasmuch as it requires removal of an arterial blood sample. Although there are potential errors in CO-oximetry measurements, produced by the presence of abnormal hemoglobins or dyes, changes in oxygenation of the sample after withdrawal but before measurement, and other factors, CO-oximetry represents a reasonable method to obtain accurate measurements of carboxyhemoglobin levels, albeit time consuming.
A better standard for measuring carboxyhemoglobin can be provided by gas-chromatographic measurements of the carbon monoxide evolved from hemolyzed blood samples treated with K3Fe(CN)6 to convert all hemoglobin to met-hemoglobin. Fogh-Andersen N, Eriksen P S, Grimsted J, Siggaard-Andersen O, Gas-chromatographic measurement of carboxyhemoglobin in blood from mothers and newborns, Clin Chem, 34:24-6 (1988)(incorporated by reference). However, gas chromatography is generally limited to research laboratories because it is complex and time consuming and requires specialized skills for proper operation.
Pulse oximeters are non-invasive monitors of arterial blood oxygen saturation. They are used to determine the fraction of oxyhemoglobin in arterial blood. The technology was developed in the 1970""s and 80""s, and has become indispensable in emergency rooms, operating rooms, and intensive care units. The instruments take advantage of the differing light absorbance spectra of oxy- and reduced hemoglobin to measure the fractional concentration of oxy-hemoglobin present in arterial blood. Mendelson Y, Pulse oximetry: theory and applications for noninvasive monitoring, Clinical Chemistry, 38:1601-7 (1992)(incorporated by reference); Hanning C D, Alexander-Williams J M, Pulse oximetry: a practical review, BMJ 311:367-70 (1995)(incorporated by reference); Lindberg L G, Lennmarken C, Vegfors M, Pulse oximetryxe2x80x94clinical implications and recent technical developments, Acta Anaesthesiol Scand, 39: 279-87 (1995)(incorporated by reference).
Pulse oximeters compute oxygen saturation (the relative amount of oxygen carried by the hemoglobin in arterial blood) by measuring differences in the visible and near infrared absorbances of fully oxygenated and deoxygenated arterial blood. Unlike clinical blood gas analyzers, which require a sample of blood from the patient and can provide only intermittent measurement of patient oxygenation, pulse oximeters provide continuous, safe and instantaneous measurement of blood oxygenation.
In conventional pulse oximeters, light produced by two light-emitting diodes (LED""s) at approximately 660 nm (red) and 940 nm (infrared) are alternately passed through the subject""s finger, toe, or ear (or other well-perfused tissue), and the transmitted light is measured by a rapidly-responding photodetector. At each of the two wavelengths, the resulting time-varying measurement of light intensity is roughly proportional to finger volume, which varies with the arterial pulsexe2x80x94a process termed xe2x80x9cphotoplethysmographyxe2x80x9d. The light which is not transmitted to the photodetector is absorbed by the finger. The amount of absorbance depends on tissue density and the amount and character of the blood (venous and arterial) that is present in the light path.
Changes in absorbance (A) are caused by changes in the amount of blood present in the light path, assumed to be primarily change in the amount of arterial blood due to the arterial pulse. Because absorbance of oxy-hemoglobin differs for light at the two wavelengths, a ratio of change in absorbance of red to change in absorbance of infrared light can be used to measure oxy-hemoglobin percentage. In practice, transmittance (T=10xe2x88x92A) is measured from each of the photoplethysmograms, which is mathematically corrected to yield absorbance. The two measurements are then electronically divided, and after inconsistent data points are discarded, the ratios are averaged to yield an average ratio of red/infrared absorbance change. The average ratio is then multiplied by a correction factor that has been empirically determined for each instrument by comparison with arterial blood samples measured with a CO-oximeter in normal subjects made hypoxemic, or in oxygen deficiency, caused by breathing gases of low fractions of inspired oxygen (FiO2).
Commercial pulse oximeters used to measure the amount of arterial blood oxygen saturation (SaO2) are available from the following manufacturers: BCI International, Biochem International, Inc., Criticare Systems, Inc., Datascope Corp., Datex Instrumentation Corp., Gambro Engstrom A. B., Invivo Research, Inc., Kontron Instruments, Life Care International, Inc., MSA, Medical Research Laboratories, Minolta Camera Co., Ltd., Nellcor-Puritan-Bennett, Nippon Colin Co., Ltd., Nonin Medical Systems, Inc., Ohmeda, Inc., Palco Labs. PhysioControl, Respironics, Inc., Sensor Medics Corp., Siemens Medical Systems, Inc., Simed Corp. and Spectramed, Inc.
Pulse oximeters can be controlled with various software packages, including those made by EMG Scientific. Signal processing apparatus, such as that disclosed in U.S. Pat. No. 5,490,505, can be used to process the signals generated by a pulse oximeter.
Prior designs of pulse oximeters used to measure arterial oxygen saturation are well known. For example, U.S. Pat. No. 4,653,498 to New, Jr. et al. (1987) describes a display monitor for use with a pulse oximeter of the type wherein light of two different wavelengths is passed through body tissue, such as a finger, an ear or the scalp, so as to be modulated by the pulsatile component of arterial blood therein and thereby indicates oxygen saturation. Similarly, U.S. Pat. Nos. 4,621,643 (1986), 4,700,708 (1987) and 4,770,179 (1988), also to New, Jr. et al., describe disposable probes for use with pulse oximeters.
One problem with pulse oximeters is that they tend to measure carboxyhemoglobin as oxy-hemoglobin. At 940 nm, oxy-hemoglobin is the predominate absorber of light, while at 660 nm reduced hemoglobin is the main absorber. Carboxyhemoglobin also absorbs strongly at 660 nm. Vegfors M, Lennmarken C, Carboxyhaemoglobinaemia and pulse oximetry, Brit J Anaesth, 66:625-6 (1991)(incorporated by reference). Thus, a reading of 100% SaO2 actually only indicates that no reduced hemoglobin is present; there may be any mixture of oxy- and carboxyhemoglobin. This eliminates pulse oximeters, as they are now manufactured, from being used as efficient instruments to detect elevated carboxyhemoglobin levels or to accurately detect the abnormally low level of oxyhemoglobin present in the blood of a patient with CO poisoning.
Adaptation of a pulse oximeter to measure carboxyhemoglobin as well as oxy- and reduced hemoglobins may be attempted by the use of three LED""s at appropriate wavelengths, perhaps 579 nm (isobestic for reduced and carboxyhemoglobins), 649 nm (isobestic for oxy- and carboxyhemoglobins), and 803 nm (isobestic for oxy- and reduced hemoglobins), to allow separation of the three hemoglobins. In that case, somewhat more complex calculations than a simple ratio of changing absorbances would have to be made by the instrument to solve three simultaneous equations with three unknowns.
Devices which use this more complex method of additional LEDs are disclosed in U.S. Pat. Nos. 4,167,331, 5,355,880 and 5,412,100. Each of these devices is complex and hindered from practical use because of the need for a third wavelength.
Other attempts have been made to measure blood constituents. For example, U.S. Pat. No. 4,407,290 (1983) to Wilber, discloses a blood constituent concentration measuring device that is capable of measuring changes in blood thickness of such constituents relative to total thickness change of blood at a test area.
Additionally, Braig et al. in U.S. Pat. No. 5,313,941 discloses a method and apparatus for measuring blood constituents by monitoring infrared absorption of the desired blood constituent in the long infrared wavelength range, between 2-20 xcexcm, preferably 9.1 xcexcm for glucose. As Braig et al. recognizes, however, the use of long wavelength infrared energy may burn or cause patient discomfort. Therefore, the Braig et al. device requires that pulses of infrared energy (two or more) are sent per heart beat. In addition to the danger to the patient, this requires a more complex mechanical device.
Complex mathematical programs for calculating blood constituent levels from multiple variants are disclosed in U.S. Pat. Nos. 5,285,782 and 5,435,309. Both of these patents contemplate complete, multi-variant readings from their devices and the requisite microprocessor power to calculate the necessary algorithms.
Tehrani U.S. Pat. No. 4,909,259 teaches the determination of a subject""s metabolic rate through the combined use of a CO2 analyzer and an O2 analyzer or a pulse oximeter to compare ratios of oxygen to carbon dioxide in the blood. Tehrani does not, however, disclose a non-invasive method for detecting carboxyhemoglobin levels in the blood.
For practical clinical purposes, met-hemoglobin and sulf-hemoglobin can be ignored in most cases. However, various mixtures of oxy-, carboxy-, and reduced hemoglobin are commonly present in smokers, fire fighters, victims of fires, tunnel workers, persons using indoor kerosene heaters or wood-burning stoves, and persons who attempt suicide by exposure to natural gas or automobile exhaust. Thus, the development of a non-invasive monitor that can separate oxy- and carboxy-hemoglobins would serve a useful purpose.
The availability of a simple, inexpensive, non-invasive monitoring device for carboxyhemoglobin would greatly simplify diagnosis, and would lead to more rapid diagnosis of CO intoxication and consequently reduced morbidity from the neurologic and cardiac sequelae. By allowing appropriate triage by paramedics, such an instrument might also lead to reduced need for emergency room visits to exclude CO intoxication in patients with suggestive symptoms.
A non-invasive carboxyhemoglobin monitor would likely find a substantial market among hospital emergency rooms, community emergency medical services, fire departments, gas companies, among others.
In accordance with the invention, the above and other objects are met by the present non-invasive monitoring device and method for analysis of blood constituents.
The present invention for analyzing and monitoring carbon monoxide levels in a patient and detecting possible carbon monoxide poisoning is a pulse oximeter which measures the changing absorbencies at two wavelengths, one of which is a wavelength at which carboxy and oxy-hemoglobins absorb light to a similar degree and the second wavelength one where carboxy and oxy-hemoglobins absorb light at a different degree, for example, at 660 nm and 940 nm, and calibrated against known carboxyhemoglobin standards. Prior to using this device on a patient, the patient breathes oxygen at a sufficient flow rate to eliminate reduced oxygen. By doing so, with the exception of very small amounts of met- and sulf-hemoglobins, the only hemoglobin components of the arterial blood are oxy- and carboxyhemoglobin, which can be distinguished at the proposed wavelengths.
Accordingly, it is an object of the present invention to provide a simple, inexpensive, non-invasive monitoring device for carboxyhemoglobin.
It is another object of this invention to provide a device and method for simplifying diagnosis of CO intoxication and consequently reduce morbidity from the neurologic and cardiae sequelae.
It is another object of the present invention to provide a device and method for diagnosing CO intoxication which allows use on-site by paramedics and other emergency personnel, thus reducing the need for emergency room visits to exclude CO intoxication with suggestive symptoms.
Yet another object of the present invention is to provide accurate carboxyhemoglobin measurements using only 2 LEDs.
Another object of the present invention is to provide a device capable of working in and switching between two modes, the first as a conventional pulse oximeter and the second mode capable of determining levels of carboxyhemoglobin.